USPTO Patents Application 09899372

REMARKS

L Status of the Claims

Claims 69-92 and 94-96 have been withdrawn from consideration as drawn to non-
elected species. Claims 55-65 and 67-96 are currently in the case.
IL Objection to the Specification

The Actions objects to the Specification on the ground that essential material is
incorporated by reference from pending applications 08/979,456, 08/979,526, and 09/198,998,
and that there is an attempt to incorporate this material that is allegedly ineffective.

Applicant assumes the Examiner is referring to the paragraph beginning on page 9, line 8
that continues on page 9, and the paragraph immediately following, which refer to the
applications mentioned in the Action. Applicant submits that the disclosures of these three
applications are properly incorporated by reference in the originally filed application in the first
paragraph, on page 1 of the application. Applicants request, therefore, withdrawal of the
objection to the specification., and fiirther note that should the addition to the present application
of material from any of these applications be deemed to be necessary, that such addition would
not constitute new matter. (MPEP 2163.07(b))
III. Rejections Under 35 USC §112

The Action rejects claims 55-65, 67, 68, and 93 under 35 USC 112, first paragraph for
lack of written description for the claims element "about 90% of said water soluble peptides are
between about 300 and about 1300 daltons in molecular weight."

Applicant respectfiiUy traverses in that the specification provides more than adequate
written description for the claim element. First, as stated in the Action, the claim element is in
the originally filed claims, both in the present application and in the parent. It is established

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patent law that "original claims constitute their own written description.) In re Koller, 613 F2d
819, 204 USPQ 702 (CCPA 1980) (MPEP 2163).

The Specification provides further support at the paragraph at the bottom of page 8 and
top of page 9. This paragraph describes the characteristics of the peptides and the analysis of the
molecular weight based in part on the data in Figure 1. The claim element is a reasonable
assessment of the molecular weight of those peptides based at least in part on the data of Figure
1. As such, one of skill in the art would fully understand that the inventors had possession of the
invention of claim 55 at the time of filing of the present application, as well as at the time of
filing of the parent. The Specification thus contains more than adequate written description for
the claims and Applicant respectfiiUy requests that this rejection be withdrawn.

Claims 55-65, 67 and 68 are also rejected under §112, first paragraph for alleged lack of
enablement for any composition other than a topical composition. Applicants respectfully
traverse on the ground that the Specification fially enables one of skill in the art to produce the
claimed peptides. The claimed peptide compositions, which the Action acknowledges as being
novel and as having at least one utility, for use in topical formulations, is fiilly enabled.

Applicant does not agree with the Action's assessment of the nature of the invention. The
invention of claim 55 is the powdered peptide composition. The composition is shown in the
application to have useful bioactivity. The Action's interpretation of the invention as limited to a
topical composition reads a limitation into the claims that is not there.

The cases cited by the Action are not relevant to the present claims. For example, the
Action states that "in cases involving chemicals and chemical compounds that differ radically in
their properties. . . that the chemicals or chemical compositions included in the claims are capable
of achieving the desired result." (emphasis added) Applicant submits that the present claims are
not drawn to chemicals or chemical compounds that differ radically in their properties, but rather

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are drawn to a composition of keratin peptides that are shown in the Specification to have
bioactivity.

The issue here is not whether the Specification enables all compositions to which the
peptide composition can be added, but rather, the enablement of the peptide composition
independent of adding it to a particular type of carrier. The Specification contains more than
adequate description of how to obtain the peptide composition and also teaches how to use the
composition to stimulate growth of usefiil cell types. Nothing more is required for enablement of
the claims. Applicant submits, therefore, that this rejection is improper and requests that the
rejection be withdrawn.

IL Claim rejections under 35 U.S,C, §103

Applicant submits that none of the cited references teaches or suggests the claimed
inventions. The Action cites several references that refer to keratin and keratin products. None of
these references, however, describes the peptide compositions of the present claims. The present
application arises fi-om the surprising discovery that after a mild oxidation of hair, a water
soluble portion of the oxidized product contains a fi-action of peptides that have bioactivity. This
fraction was discovered by subjecting a neutralized solution of oxidized keratin protein to
alcohol precipitation at a concentration at which low molecular weight peptides precipitate from
solution. These peptide compositions were then shown to have the ability to stimulate growth of
cells that are involved in wound healing. None of the cited keratin art suggests the presence of
these low molecular weight peptides in a keratin preparation, but rather describe larger molecular
weight fractions of MW 30,000 and above. In those references in which some wound healing
properties are described for keratin compositions, there is no suggestion that the claimed low
molecular weight fraction exists, or that such a fraction, if it did exist would exhibit woxmd
healing properties. The only low molecular weight keratin product described is a hydrolysate in

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which either harsh reaction conditions or enzymes are used to break the peptide bonds of the
protein backbone. In contrast, the conditions under which the claimed peptide compositions are
produced are chosen to minimize such hydrolysis.

The Action also cites a reference describing peptides isolated from milk proteins. There is
no suggestion and no reason to believe that the milk peptides are in any way related to the keratin
peptides of the claims. There is also suggestion in the reference that similar sized peptides from
any other source would have a similar activity to those isolated from milk proteins. There is no
motivation to combine this reference with the description of peptide compositions from any other
source. The Examiner has thus failed to make a prima facie case of obviousness and the
rejections under § 1 03 should be withdrawn.

The claimed compositions are neither taught nor suggested by the 473 patent.

The Action rejects claims 55-65, 67, 68, and 93 as obvious over US 4,495,173, taking the
position that the product produced by the method described in the '173 patent could have a
molecular weight of 200-5000. Applicant does not agree that the oxidized composition described
in the '173 patent could have a molecular weight of 200-5000, as the '173 patent states that is has
a molecular weight of 30,000-100,000 (col 5, line 47).

The Action states that the '173 patent describes oxidizing human hair, feathers etc with
peroxide or peracetic acid followed by neutralization and gel filtration. Applicant assumes the
Action is referring to the method described as method (1) Oxidation and Decomposition
Reaction in column 2, beginning on line 31. The reaction described is carried out in an excess of
oxidizing agent such that all the disulfides are oxidized to sulfonic acids. The '173 patent also
states at column 5, line 45

The decomposition products obtained by the method (1) or (2) should preferably have an
average molecular weight of 30,000-100,000 and those obtained by the method (3) should

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preferably have an average molecular weight of 200-5,000. The 473 patent thus teaches away
from the claimed invention, teaching that the oxidation method produces a product of 30,000-
100,000 molecular weight. Nowhere does the '173 patent suggest that a low molecular weight
fraction is produced by this method, nowhere does the 473 patent teach of suggest a peptide
fraction of from 300-1300 daltons, and nowhere does the 473 patent suggest that such a fraction,
if it did exist, would have bioactivity. The Examiner has thus failed to make a prima facie case of
obviousness and this rejection should be withdrawn.

This oxidative method is again discussed in the 473 patent in Synthetic Example 1
column 9, line 10. In the example, the wool is oxidized, filtered and then dissolved in ammonia
solution. The product is then taken to pH 4 "whereupon a-keratose was settled as a
precipitate." (emphasis added) As discussed in the response to the previous Office Action, a-
keratose is a known fraction of molecular weight 30,000-60,000 that is insoluble at low pH. This
fraction is thus precipitated by bringing the solution to pH below 4. This is a different fraction
than the low molecular weight peptides that are precipitated by alcohol as described in the
present application and claims. The Examiner has ignored the acid precipitation step and instead
has chosen certain steps from the oxidation method (method (1) of the 473 patent) and combined
them with results from the enzymatic degradation method (method (3) of the 473 patent) in an
attempt to reconstruct Applicant's invention in hindsight.

Turning to the enzymatic process, (process (3)) the 473 patent teaches that hydrolysis
with an enzyme, with strong acid, and in strong base, all resulted in peptide fractions in which
the disulfide bonds were intact, in contrast to the oxidation method (1) in which all the cystines
were converted to sulfonic acid. That alone is a chemical characteristic that distinguishes the
claimed compositions from the hydrolysates of the 473 patent. Furthermore, a peptide
composition with an average molecular weight of from 200-5,000 does not suggest the

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composition of the present claims, in which at least 90% of the peptides have a molecular weight
of from 300-1300, with an average of about 850 daltons. And again, there is no suggestion in the
'173 patent that the hydrolysates have any bioactivity. The Action states that the process of
production does not impart patentability, but that is a moot point since the peptide compositions
of the present claims are not anticipated by the cited art.

Applicants submit therefore, that the 473 patent can in no way be said to teach or suggest
the claimed inventions, that the '173 patent teaches away from the claimed invention, and that all
rejections over the '173 should be withdrawn.

The claimed compositions are neither taught nor suggested by the *138 patent.

The Action also rejects claims 55-65, 67, 68, and 93 as obvious over 5,276,138 ('138) in
view of 6,506,732 ('732). Applicant traverses and finds no description or suggestion of the
present invention in the cited references.

The '138 patent has been addressed in the response to the previous Office Action. The
patent describes a composition containing a-keratose. a-keratose is an acidic portion of the
oxidized hair that is insoluble at low pH, and thus precipitates in acid. This fraction has a much
higher molecular weight than the peptides precipitated by ethanol at neutral pH as described in
the present specification and claims. Figure 1 of the '138 shows the molecular weight, which has
a peak around 30-40,000. Even if the peptides of the present claims were contained within the
composition with the larger peptides of the '138 preparation, there is no way to know that from
reading the patent. There is also no suggestion in the patent that there is a low molecular weight
fraction that could be isolated, or that any fraction of this preparation would have the cell growth
activity of the claimed compositions.

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The U38 reference does not suggest that any useful fraction of peptides can be

precipitated from a soluble preparation of oxidized hair. The 438 does teach that a fraction can

be precipitated by lowering the pH of the solution to below 4. For example,

As previously stated, the present invention relates also to the
process for recovering the solubilized product of the animal hairs
which comprises admixing the solution of said product with an
organic acid or an aqueous solution thereof to precipitate said
product. CI 38) colunm 4, lines 29-33

Under normal conditions, the pH of the mixed system of the
solution of the solubilized product of the animal hairs and the
organic acid may be adjusted less than about 4.5, preferably 1-4. If
the pH of the mixed system if more than 4.5, the solubilized
product of the animal hairs becomes hard to precipitate, (col. 4,
lines 58-63)

Thus the '138 reference also teaches away from the present claims, by teaching that the
composition cannot be precipitated at pH above 4.5, and yet the claimed peptides are precipitated
at neutral pH. Thus the claims are clearly distinguished from the disclosure of '138, both in the
process of obtaining them and in their molecular weight, not just because of the process step
alone, but because the different chemical characteristics of the two peptide compositions cause
them to precipitate under different conditions.

Although the '138 patent discusses the use of a polar solvent such as alcohols, acetone
and the like, this step is used to further purify the a-keratose that was the result of a previous
acid precipitation and to "remove trace amounts of stinking components of low molecular
weight, colored substances and the like contained in the solubilized product solution of the
animal hairs," (col 5, line 24)and not to isolate a bioactive subfraction of peptides. The '138 can
thus in no way be said to teach or suggest the present claims, and teaches away from the present
claims by teaching precipitation from aqueous solution at low pH, and by teaching that only trace
amounts of useless contaminants can be removed from the a-keratose preparation by washing

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with aqueous solution of organic acids and/or volatile organic solvents. Therefore, the low
molecular weight peptides would not meet the objects of the *138 disclosure. According to
M.P.E.P. 2143.01, if, as in the present case, a modification would render the prior art invention
being modified unsatisfactory for its intended purpose, then there is no suggestion or motivation
to make the proposed modification. In re Gordon, 733 F.2d 900, 221 USPQ 1125 (Fed. Cir.
1984). Applicant requests therefore, that all rejections over '138 be withdrawn.

All rejections over '138 in view of 732 should be withdrawn as the references are
not combinable and would not reach the claimed inventions even if combined.

The disclosure of the 732 patent in no way overcomes the deficiencies of the 438
reference as applied to the claimed inventions. The Examiner has completely failed to make a
prima facie case of obviousness for the combination of references. The 732 reference describes
compositions including peptides derived fi*om milk proteins that are totally unrelated to the a-
keratose described in '138. The Examiner has pointed to nothing in the references that would
suggest any combination or any reason to modify the disclosures of either reference for such a
combination.

Establishing prima facie obviousness requires a showing that each claim element is
taught or suggested by the prior art. See In re Royka, 490 F.2d 981, 180 USPQ 580 (CCPA
1974). Specifically, establishing prima facie obviousness requires a showing that some
combination of objective teachings in the art and/or knowledge available to one of skill in the art
would have lead that individual to arrive at the claimed invention. See In re Fine, 5 USPQ2d
1596,1598 (Fed. Cir. 1988). Moreover, establishing prima facie obviousness requires not only a
showing that such a combination of prior art teachings is possible, but also that the teachings
would have 1) motivated the skilled artisan to make the combination to arrive at the claimed
invention, and 2) suggested to the skilled artisan a reasonable likelihood of success in making

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and using the claimed invention. See In re Dow Chem, Co,, 837 F.2d 469, 473 (Fed. Cir. 1988).
Absent a showing of such motivation and suggestion, pr/Awa facie obviousness is not established.
See Fine, 5 USPQ2d at 1598. Additionally, the teaching or suggestion to make the claimed
combination and the reasonable expectation of success must both be foimd in the prior art, and
not based on applicant's disclosure. In re Vaeck, 947 F.2d 488, 20USPQ2d 1438 (Fed. Cir. 1991)

Therefore, even if the references were to teach every element of the claimed invention,
which they do not, without a motivation to combine the references, there is no prima facie case
and no burden on Applicant to present evidence of non-obviousness. The Action appears to take
the position that any peptide is equivalent to any other peptide of the same or similar molecular
weight regardless of the source or the amino acid sequences. Otherwise there would be no
connection between the 732 disclosure and the present claims, and even given that erroneous
idea, there is no connection between the '138 and 732 references except they both describe
peptide compositions.

Tuming to the 732 patent. Applicant finds no suggestion in the reference that one should
modify the processes to oxidize disulfide bonds as in the '138 patent. Applicant finds no mention
of disulfide bonds at all in the '732, or any other reason to oxidize the proteins in order to isolate
the described peptides. The '732 rather describes enzymatic hydrolysis with pepsin and
chymotrypsin in order to obtain peptides with specific characteristics. There is no suggestion in
the '732 that the same or similar peptides could be obtained firom hair, firom an isolated a-keratin
fi"action as described in '138, or any other keratin source. Applicant finds, therefore, no
motivation to combine the references, and no understanding of how such a combination would
arrive at the claimed invention.

Because the '138 and '732 references do not teach every element of the claims, contain no
motivation within their respective disclosures to combine the teachings of the references in any

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way, and further because one of skill in the art would have no expectation of succeeding in
arriving at the claimed inventions in making such a combination, the current rejection is
improper. Applicant respectfully requests that all rejections over '138 and 732 either separately
or in combination be withdrawn.

The '583 patent does not describe or suggest any of the process steps in the claims
nor any peptide product of the claims and can in no way be said to teach or suggest the
claimed inventions.

The Action rejects claims 55-65, 67, 68, and 93 as obvious over US Patent No. 5,763,583
('583) in view of 732. The Action states that *583 teaches a water soluble protein . , . produced by
oxidation, neutralization of the produced aqueous solution, followed by filtration, and the use of
organic solvents. Applicant traverses and submits that this is nothing more picking out process
steps in an attempt to reconstruct Applicant's claims with no regard for how or when those steps
are used and for what pxirpose in the production of the products of the '583 reference. For
example, the only use of organic solvents is for solutions of plasticizers for making films as
described in col 5 and in Example 4 for the same purpose. There is no way that the use of an
organic solvent as described in '583 is equivalent to, or in any way suggests the precipitation of
low molecular weight peptides from aqueous solution in alcohol as in the present claims.

Furthermore, the '583 does not describe "oxidizing hxmian or animal hair, human or

animal nails, fiir, hooves, or feathers, in an aqueous oxidizing solution" as in claim 55, but rather

instead describes oxidation of the thioglycolate groups boimd to the protein by the previous

reduction of the cystine disulfide bonds.

In accordance with the present invention, disulfide bonds (-SS-) in
the disulfide bond-containing water-insoluble protein are reduced
into mercapto groups (-SH) and a part or entire portion of the
mercapto groups is subsequently converted into
carboxymethyldisulfide groups (-SSCH2COOH), whereby the
solubilized protein is obtained, (col 2, line 49)

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The product of the reduction and oxidation reactions in *583 may be filtered to remove
insoluble materials, but the patent also teaches that the product is dialysed to remove any
molecules with a molecular weight under 10,000. (col. 4, line 16-20, col. 6, lines 47-49, col. 7,
lines 14-17, col. 8, lines 25-28) This results in protein products having molecular weights of
40,000-60,000, (col 4, line 30) 40,000-80,000 (Examples 1 and 2) The dialysis step thus removes
and discards any peptides that would fall within the claimed compositions in the present
application. This is a desired object of the *583 disclosure to remove low molecular weight
products. As stated in col. 4, lines 30-33, no lower molecular weight products were detected in
the SDS gels. Additionally, the first paragraph in Colunm 2 states that it is an objective of the
invention to "maintain the molecular weight and the a-helix structure of the keratin protein." The
*583 thus also teaches away firom the claimed invention by teaching the benefit of products that
exclude the peptide products of the instant claims.

Any attempt to combine the *583 with the 732 disclosure suffers the same deficiencies as
discussed above for the combination with *138. The references are unrelated and contain no
direction of motivation for any combining of the teachings. The Examiner has simply failed to
make any kind of credible case for obviousness. Applicant respectfiiUy requests that all
rejections over the *583 alone or in combination with other references be withdrawn.

The *552 patent does not teach or suggest the elements of the present claims and
teaches away from any composition of low molecular weight peptides.

The Action rejects claims 55-56, 67, 68, and 93over US 5,932,552 in view of 732, taking
that position that the description of certain process steps that appear in the claims renders those
claims obvious. Applicant respectfiiUy traverses on the groxmd that following the processes

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described in the '552 patent result in a very different product that in no way suggests, but rather

teaches away from the present claims.

The '552 reference again describes protein fractions from keratin containing materials

that are of much higher molecular weight than those of the present claims. The peptides of the

present claims would, in fact, be inoperable in the practice of the '552 patent, as no hydrogel can

be formed from the low molecular weight peptides of the present claims. The Examiner's

attention is drawn to the description in columns 3 and 4. The hair is oxidized and filtered to

remove the insoluble materials and dried (col 3, lines 47-65). The soluble material is then

reduced with ammonium thioglycolate at high pH (3N ammonium hydroxide). This step is

totally ignored by the present Action. After this step the solution is again filtered to remove the P

fraction (col. 4, line23). The next step is also ignored by the present Action.

The supernatant is purified, using a method such as dialysis. A
preferred method uses dialysis against running water using a
dialysis membrane (Spectra/Por TM) having a cutoff of about 8000
MW. (col. 32-35)

The '552 thus teaches that anything below 8000 molecular weight is discarded, sent down
the drain with the running water from the dialysis. The reference thus clearly teaches away from
the present claims and is not combinable with any of the other cited references to make a case for
obviousness against the present claims. Applicant respectfijUy requests that all rejections over
'552 be withdrawn.

In light of the preceding discussion, the Examiner has completely failed to make a prima
facie case of obviousness and Applicant respectftiUy requests that all rejections under §103 be
withdrawn.

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Conclusion

In light of the preceding discussion, all pending claims are in condition for allowance and
an early indication of such is respectfully requested. Applicant further requests that the
withdrawn claims be rejoined to the Application in the allowance. If the Examiner has any
questions or suggestions, she is invited to call to the undersigned representative at 512.542.8446.

First City Tower

1001 Fannin, Suite 2300

Houston, Texas 77002-6760

512.542.8446

Date: September 7, 2005

Respectfully submitted,

Vinson & Elkins L.L.P.

Timothy S, Corder
Reg. No. 38,414
Agent for Applicants

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